N-Methyl-2-{3-methyl-2-[(2Z)-pent-2-en-1-yl]cyclopent-2-en-1-ylidene}hydrazinecarbothioamide

The synthesis, crystal structure and Hirshfeld analysis of cis-jasmone 4-methylthiosemicarbazone is reported. Two crystallographically independent molecules are observed in the asymmetric unit, one of them being disordered over the carbon chain. In the crystal, the molecules are linked by N—H⋯S and C—H⋯S interactions into independent centrosymmetric dimers.

The equimolar and hydrochloric acid-catalysed reaction between cis-jasmone and 4-methylthiosemicarbazide in ethanolic solution yields the title compound, C 13 H 21 N 3 S (common name: cis-jasmone 4-methylthiosemicarbazone).Two molecules with all atoms in general positions are present in the asymmetric unit.In one of them, the carbon chain is disordered [site occupancy ratio = 0.821 (3):0.179(3)].The thiosemicarbazone entities [N-N-C(=S)-N] are approximately planar, with the maximum deviation from the mean plane through the selected atoms being À 0.0115 (16) A ˚(r.m.s.d.= 0.0078 A ˚) for the non-disordered molecule and 0.0052 (14) A ˚(r.m.s.d.= 0.0031 A ˚) for the disordered one.The molecules are not planar, since the jasmone groups have a chain with sp 3 -hybridized carbon atoms and, in addition, the thiosemicarbazone fragments are attached to the respective carbon five-membered rings and the dihedral angles between them for each molecule amount to 8.9 (1) and 6.3 (1) � .In the crystal, the molecules are connected through pairs of N-H� � �S and C-H� � �S interactions into crystallographically independent centrosymmetric dimers, in which rings of graph-set motifs R 2 2 (8) and R 2 1 (7) are observed.A Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are from H� � �H (70.6%),H� � �S/S� � �H (16.7%),H� � �C/C� � �H (7.5%) and H� � �N/N� � �H (4.9%) interactions [considering the two crystallographically independent molecules and only the disordered atoms with the highest s.o.f. for the evaluation].

Structure description
To the best of our knowledge, the first crystal structure of cisjasmone thiosemicarbazone was reported recently and it was pointed out that this derivative based on non-substituted cisjasmone shows antifungal activity (Orsoni et al., 2020;Jamiołkowska et al., 2022).
As part of our interest in thiosemicarbazones attached to natural product derivatives and on the influence of the substituent groups at the terminal N atom on the supramolecular arrangement, we report here the synthesis, crystal structure and Hirshfeld analysis of cis-jasmone 4-methylthio-semicarbazone.It is important to highlight that the substituents at the terminal N atom are relevant not only to the crystal packing, but also to the biological properties of the thiosemicarbazone derivatives.For example, a small chemical library of 4-methylthiosemicarbazones has been studied for the treatment of Parkinson's disease (Mathew et al., 2021) Table 1 Selected geometric parameters (A ˚, � ) for the two crystallographically independent cis-jasmone 4-methylthiosemicarbazone molecules, JMTSC-1 and JMTSC-2.

Compound Atom chain Torsion angle Atom chain Torsion angle
The asymmetric unit of the title compound comprises two molecules with all atoms in general positions, with one of them showing disorder over the carbon chain [site occupancy ratio = 0.821 (3):0.179(3)].The molecules are not planar due to the chain with sp 3 -hybridized carbon atoms in the jasmone fragment and the dihedral angles between the thiosemicarbazone fragment and the respective carbon five-membered ring, which amount to 8.9 (1) � for the non-disordered molecule and 6.3 (1) � for the disordered one (Fig. 1).To simplify the structure description, the non-disordered molecule, with atoms C1-C13/N-N3/S1, will be designated as JMTSC-1, while the disordered one, with the atoms C14-C23A/C23B/ N4-N6/S2, will be designated as JMTSC-2.To get a stable refinement, the C20, C21, C22 and C23 atoms were split into two positions and A-labelled for the higher s.o.f and B-labelled for the lower.Atom C19, which is itself not disordered, is bound to C20A and C20B, and to achieve the best orientations for the C19-H bonds, the H19A and H19B atoms were also split, into two positions.Thus, the H19A and H19B atoms have a s.o.f. of 0.821 (3) and the H19C and H19D atoms have a s.o.f. of 0.179 (3).Selected geometric parameters for the structural description of JMTSC-1 and JMTSC-2 are given in Table 1; these are in agreement with literature data (Oliveira et al., 2016;Rocha et al., 2014).
For the supramolecular arrangement and Hirshfeld analysis, for clarity only the disordered atoms with the highest s.o.f.value were considered.In the crystal, the molecules are connected through pairs of N-H� � �S and C-H� � �S interactions into centrosymmetric dimers with graph-set motifs R 2 2 (8) and R 1 2 (7) (Table 2).With the coordinates that were used for the refinement, the crystallographically independent dimers of the JMTSC-1 molecules have the gravity centre located in the cell vertices (Fig. 2), and in the centre of the ac planes for the JMTSC-2 molecules (Fig. 3).In addition, the molecules are stacked along [100] and only weak intermolecular interactions, e.g., London dispersion forces can be presumed in this direction (Fig. 4).
The Hirshfeld surface analysis (Hirshfeld, 1977), the graphical representations and the two-dimensional Hirshfeld surface fingerprints (HSFP) were evaluated with the Crystal Explorer software (Wolff et al., 2012) and 3).The contributions to the crystal cohesion are shown as two-dimensional Hirshfeld surface fingerprint plots (HSFP) with cyan dots (Fig. 6).
The crystalline supramolecular arrangement of thiosemicarbazones depends on the template effect of the crystallization solvent, the presence of solvate molecules and on the crystallization methods.In addition, the steric effect of the substituents in the R 1 R 2 N-N(H)-C(=S)-NR 3 R 4 fragment is of prime importance for the crystal packing.In the title compound, two structural features lead to the building of dimers.The first one is the terminal methyl group, N(H)CH 3 , which decreases the possibility for N-H� � �S intermolecular interactions and enhances the formation of hydrogen-bonded supramolecular structures.On the other side of the molecule, the second feature is the cis-jasmone entity, which, through steric hindrance, precludes intermolecular interactions, e.g., N-H� � �S or N-H� � �N (Figs. 2 and 3); thus, four methylsubstituted thiosemicarbazone derivatives were selected for structural comparison with the title compound.
The first example is the crystal structure of benzylideneacetone 4-methylthiosemicarbazone (Rocha et al., 2014).As a result of the steric effect of two methyl groups, one on the terminal N atom and other on the C atom attached to the thiosemicarbazone entity, dimer formation was favoured.The remaining N-H bond is involved in the N-H� � �N intramolecular interaction, with graph-set motif S(5).Thus, the molecules are linked by N-H� � �S interactions, with graph-set motif R 2 2 (8), into centrosymmetric dimers.For the graphical representation of the dimeric unit, see Fig. 7(a).
The second selected molecule is the vanilline 4-methylthiosemicarbazone derivative (Oliveira, Beck et al., 2015) in which the thiosemicarbazone entities are connected by N-H� � �S interactions, with graph-set motif R 2 2 (8), into centrosymmetric dimers.The dimers are further linked through N-H� � �S and O-H� � �S interactions and can be considered subunits of a hydrogen-bonded tape-like supramolecular arrangement.This is only possible because of the O atoms in the vanilline structure, see Fig. 7

(b).
A further example is 3 0 ,4 0 -(methylenedioxy)acetophenone 4-methylthiosemicarbazone (Oliveira, Na ¨ther et al., 2015).As mentioned above, the terminal methyl group decreases the dimensionality of the molecular arrangement and the thiosemicarbazone entities are connected by pairs of centrosymmetric N-H� � �S interactions, with graph-set motifs R 2 2 (8).A feature of the structural arrangement of this compound is that every thiosemicarbazone fragment bridges two other mol-ecules through N-H� � �S interactions in opposite directions, see Fig. 8(a).
Finally, the structure of (-)-menthone 4-methylthiosemicarbazone (Oliveira et al., 2016) shows a non-centrosymmetric dimer, with the molecules connected by pairs of N-H� � �S interactions, also with graph-set motif R 2 2 (8).A difference in this structure is the linking of the terminal N-H bonds between the molecules through N-H� � �S interactions into a tape-like structure.For the dimeric subunit of the supramolecular arrangement, see Fig. 8(b).
As observed for the title compound, pairs of N-H� � �S intermolecular interactions with graph-set motif R 2 2 (8) are a remarkable feature for the crystal structure of thiosemicarbazone derivatives.The supramolecular arrangement of the compounds depends on the structure of the substituents on the terminal N atom, as well as on the fragment attached to the first N atom.

Synthesis and crystallization
The starting materials are commercially available and were used without further purification.The synthesis of the cisjasmone 4-methylthiosemicarbazone derivative was adapted from previously reported procedures (Oliveira, Beck et al., 2015;Orsoni et al., 2020).A mixture of ethanolic solutions of cis-jasmone (8 mmol in 50 ml) and 4-methylthiosemicarbazide (8 mmol in 50 ml) was catalysed with HCl and refluxed for 8 h.After cooling, the precipitated product was filtered off and washed with cold ethanol.Colourless single crystals suitable for X-ray diffraction were obtained from tetrahydrofuran by slow evaporation of the solvent at room temperature.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3.There are two crystallographically independent molecules in the asymmetric unit of the title compound and one of them, JMTSC-2, shows disorder over the chain of the cis-jasmone fragment, namely the C20, C21, C22, C23, H19C and H19D atoms (Fig. 1).These atoms were split over two positions, with the carbon atoms being Alabelled for the higher s.o.f.value positions and B-labelled for the lower [site-occupancy ratio = 0.821 (3):0.179(3)].The atom C19 is itself not disordered, but it is bound to C20A and C20B, and to get the best orientations for the C19-H bonds, the hydrogen atoms were disordered.Thus, H19A and H19B have the positions with higher s.o.f., while H19C and H19D have the positions with the lower.The EADP command was used to constrain the displacement parameters of the disordered carbon atoms.
The H atoms were treated by a mixture of constrained and independent refinement.The constrained H atoms were located in a difference-Fourier map, but were positioned with idealized geometry and refined using a riding model.For the C13H 3 , C23AH 3 , C23BH 3 and C26H 3 groups, the methyl H atoms were allowed to rotate but not to tip to best fit the experimental electron density, with U iso (H) = 1.5 U eq (C), and ] and (b) section of the molecular arrangement of the (-)-menthone 4-methylthiosemicarbazone structure (Oliveira et al., 2016).The molecules are connected by pairs of N-H� � �S interactions, with graph-set R 2 2 (8), into non-centrosymmetric dimers and further linked by additional N-H� � �S interactions, forming a tape-like structure.Only the subunit of the supramolecular arrangement is shown for clarity [Symmetry codes: (i) the C-H bonds were set to 0.96 A ˚.In an analogous manner, with U iso (H) = 1.2 U eq (C), for the C22AH 2 and C22BH 2 groups the C-H bond lengths were set to 0.97 A ˚and for the C20AH, C20BH, C21AH and C21BH, were set to 0.93 A ˚.In addition, the C19-H bonds were set to 0.97 A ˚.The remaining H atoms were refined freely.Computer programs: COLLECT (Nonius, 1998), HKL DENZO and SCALEPACK (Otwinowski & Minor, 1997), SIR92 (Altomare et al., 1994), SHELXL2018/3 (Sheldrick, 2015), DIAMOND (Brandenburg, 2006), Crystal Explorer 3.1 (Wolff et al., 2012), WinGX (Farrugia, 2012), publCIF (Westrip, 2010) and enCIFer (Allen et al., 2004).

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.

Figure 2
Figure 2 Crystal structure section of the title compound for the JMTSC-1 molecule, showing the hydrogen-bond intermolecular interactions as dashed lines.The molecules are linked into centrosymmetric dimers via pairs of N-H� � �S and C-H� � �S interactions with graph-set motifs R 2 2 (8) and R 1 2 (7).[Symmetry code: (i) À x, À y, À z + 2.]

Figure 5
Figure 5Hirshfeld surface graphical representation (d norm ) for the two crystallographically independent molecules of the title compound.The surface is drawn with transparency, and the disorder is not shown for clarity.The regions with strongest intermolecular interactions are shown in red (d norm range: À 0.216 to 1.522 a.u.).

Figure 6 The
Figure 6 The Hirshfeld surface two-dimensional fingerprint plot for the title compound, showing the contacts in detail (cyan dots).The major contributions of the interactions to the crystal cohesion amount to (a) H� � �H (70.6%),(b) H� � �S/S� � �H (16.7%),(c) H� � �C/C� � �H (7.5%) and (d) H� � �N/N� � �H (4.9%).The d i (x-axis) and the d e (y-axis) values are the closest internal and external distances from given points on the Hirshfeld surface contacts (in A ˚). Regarding the disorder, only the atoms with the highest s.o.f. were considered.

Table 3
Experimental details.